Memories for emotional episodes are intricately associated with our autobiographical experience, yet little is known about the brain mechanisms involved in encoding and retaining emotional events in memory. The proposed research uses modern cognitive neuroscience techniques to reveal insights into the organization of large-scale brain networks that link emotional stimuli to long-term memory functions. To achieve this aim, psychophysiological, event-related potential (ERP), and functional magnetic resonance imaging (fMRI) methods will be used to investigate the neurophysiological impact of emotional cues during memory encoding and retrieval tasks in normal human subjects. New techniques will be applied to improve the fMRI signal in frontolimbic brain areas and to infer their time course of activation. The spatial and temporal information obtained across parallel ERP and fMRI studies will be combined to specify how limbic forebrain areas sensitive to emotional salience manipulations dynamically interact with cortical networks specialized for mnemonic and perceptual processes. It is hypothesized that the ventromedial prefrontal cortex and amygdala will modulate activity in sensory association cortex in response to arousing stimuli. As a result, emotional events will receive enhanced stimulus binding and facilitated retrieval from memory-related areas in the medial temporal lobe and prefrontal cortex. The modality specificity of the emotional network components will be interrogated, and the brain activation patterns will be correlated with peripheral changes in autonomic physiology and memory scores in individual subjects. In drug addiction populations, episodic memories for prior drug intake and mnemonic associations triggered by drug-related environmental cues play an important role in motivational aspects of the addictive process and contribute to physiological adaptations underlying drug tolerance. The proposed studies may lead to new insights into understanding these effects by providing a more accurate and detailed account of the dynamic interplay between emotion and memory systems in the human brain.